High throughput mitochondrial DNA analysis identifies tumor-specific genetic alterations associated with bladder cancer. The proposed work seeks to explore several clinical issues related to bladder cancer management based on the detection of these genetic changes in primary tumors and urine. IThe specific aims of this project are: (1) to define the sensitivity and specificity of mitochondrial DNA panels for the detection of recurrent superficial bladder cancers and, (2) to preliminarily explore whether specific patterns of mitochondrial DNA alterations correlate with increased risk of disease recurrence or progression in both superficial and invasive cancers. These specific aims will be accomplished through prospective analysis of paired tumor and urine specimens obtained from patients with superficial and invasive bladder cancers undergoing therapy with curative intent at The Johns Hopkins Hospital and The Bayview Johns Hopkins Medical Center. The analyses will be performed using molecular methods and technology developed in projects #1 and 2. The larger goal of this project is to lay a practical foundation for future studies of mitochondrial DNA analysis for monitoring and for the establishment of risk profiles for patients with different stages of bladder cancer.